Men who have sex with men (MSM) are 44 times more likely to contract HIV than other men and they are among the only populations in which infections are on the rise. Pre-Exposure Prophylaxis (PrEP) in the form of once-daily Truvada (Emtricitabine/Tenofovir) is among the most promising biomedical prevention tool for MSM in the US. HIV-negative MSM who use club drugs (ketamine, MDMA/ecstasy, GHB, cocaine, methamphetamine) might benefit from the added protection of PrEP because our previous research found strong associations between club drug use and condomless anal sex among MSM. Further, there is substantial research, including that collected by our research team, suggesting that club drugs negatively impact HIV medication adherence for HIV-positive MSM. However, to date, there are no published equivalent studies on the role of club drugs in PrEP adherence among MSM who are taking PrEP. Instead, much data on barriers to PrEP adherence are based on hypothetical situations and/or with individuals who have never taken PrEP. The proposed study will follow two cohorts of MSM on PrEP: n = 50 who use club drugs and n = 50 who do not. Participants will be identified via our partnerships with providers who prescribe PrEP as well as those who provide other community-based services to MSM on PrEP, in addition to traditional venue-based recruitment and Internet social networking (e.g., advertising on Facebook, Grindr). AIM 1: Compare levels of PrEP adherence between MSM who use club drugs and those who do not (between-group analyses). AIM 2: Gather pilot data to identify the role that club drug use (frequency, drug type, drug combinations) plays in daily PrEP non-adherence among MSM who are drug users (within-group analyses). Measures will include self-report (retrospective via 30 day time-line follow back interview and prospective via twice-weekly online diaries for 10 weeks), biological (urine drug and oral HIV testing), objective (Wisepill Event Monitoring Device for 10 weeks), and qualitative assessments. Psychosocial and demographic measures will also be collected via ACASI at baseline, giving this study the added benefit of being able to identify other factors that are associated with PrEP non-adherence (Sub-aim 1). Given the role that club drugs play in condomless anal sex among MSM, HIV-negative MSM club drug might benefit from the added protection of PrEP. Meanwhile, there are no published studies on the role that club drugs play in PrEP non-adherence, in spite of compelling evidence that club drugs impact HIV medication adherence among HIV-positive MSM. The results of this study will be used to inform subsequent intervention strategies to reduce club drug use among MSM who take PrEP, as well as improve PrEP adherence. Consistent with the R21 mechanism, this study will generate the necessary formative pilot data for an R01 that will seek to reduce club drug use and improve PrEP adherence.